Kumada Hiromitsu, Suzuki Yoshiyuki, Ikeda Kenji, Toyota Joji, Karino Yoshiyasu, Chayama Kazuaki, Kawakami Yoshiiku, Ido Akio, Yamamoto Kazuhide, Takaguchi Koichi, Izumi Namiki, Koike Kazuhiko, Takehara Tetsuo, Kawada Norifumi, Sata Michio, Miyagoshi Hidetaka, Eley Timothy, McPhee Fiona, Damokosh Andrew, Ishikawa Hiroki, Hughes Eric
Toranomon Hospital, Tokyo, Japan.
Hepatology. 2014 Jun;59(6):2083-91. doi: 10.1002/hep.27113. Epub 2014 Apr 1.
All-oral combinations of direct-acting antivirals may improve efficacy and safety outcomes for patients with hepatitis C virus (HCV) infection, particularly those who are poor candidates for current interferon/ribavirin-based regimens. In this open-label, phase 3 study, 135 interferon-ineligible/intolerant and 87 nonresponder patients with chronic HCV genotype 1b infection were enrolled at 24 centers in Japan. Patients received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks. The primary endpoint was sustained virologic response 24 weeks after treatment (SVR24 ). This study is registered with ClinicalTrials.gov (NCT01497834). SVR24 was achieved by 87.4% of interferon-ineligible/intolerant patients and 80.5% of nonresponder (null and partial) patients; rates were similar in cirrhosis (90.9%) and noncirrhosis (84.0%) patients, and in patients with IL28B CC (84.5%) or non-CC (84.8%) genotypes. Fourteen patients in each group (12.6%) discontinued dual therapy, mainly due to adverse events or lack of efficacy. Nine nonresponder patients received additional treatment with peginterferon/ribavirin per protocol-defined criteria. The rate of serious adverse events was low (5.9%) and varied among patients. The most common adverse events were nasopharyngitis, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST), headache, diarrhea, and pyrexia.
Interferon-free, ribavirin-free all-oral therapy with daclatasvir and asunaprevir for 24 weeks is well tolerated and can achieve a high rate of SVR in patients with HCV genotype 1b who were ineligible, intolerant, or had not responded to prior interferon-based therapy. (Hepatology 2014;59:2083-2091).
直接作用抗病毒药物的全口服联合用药可能会改善丙型肝炎病毒（HCV）感染患者的疗效和安全性结局，尤其是那些不适合当前基于干扰素/利巴韦林治疗方案的患者。在这项开放标签的3期研究中，日本24个中心招募了135例不符合干扰素治疗标准/不耐受的患者以及87例无应答的慢性HCV 1b型感染患者。患者接受每日一次60mg的达卡他韦加每日两次100mg的阿舒瑞韦治疗24周。主要终点是治疗24周后的持续病毒学应答（SVR24）。本研究已在ClinicalTrials.gov注册（NCT01497834）。87.4%的不符合干扰素治疗标准/不耐受的患者以及80.5%的无应答（完全和部分）患者实现了SVR24；肝硬化患者（90.9%）和非肝硬化患者（84.0%）以及IL28B CC基因型（84.5%）或非CC基因型（84.8%）的患者中该比例相似。每组有14例患者（12.6%）停止了双联治疗，主要原因是不良事件或缺乏疗效。9例无应答患者根据方案定义的标准接受了聚乙二醇干扰素/利巴韦林的额外治疗。严重不良事件发生率较低（5.9%），且在患者中有所不同。最常见的不良事件是鼻咽炎、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）升高、头痛、腹泻和发热。
对于不符合干扰素治疗标准、不耐受或对先前基于干扰素治疗无应答的HCV 1b型患者，使用达卡他韦和阿舒瑞韦进行24周的无干扰素、无利巴韦林全口服治疗耐受性良好，且可实现较高的SVR率。（《肝脏病学》2014年；59:2083 - 2091）
